Certain phenyl-alkanoic acids are known from the literature and some of them are said to possess valuable pharmacological activities, for example, an analgesic, anti-inflammatory or anti-pyretic action, whereas others are used clinically, for example, in the treatment of rheumatoid arthritis.
However, these known phenyl-alkanoic acids suffer from certain disadvantages, due essentially to their insolubility in water, to their acidity and, to a certain extent, to their toxicity. Thus, their insolubility restricts their possibilities for use; for example, they cannot be administered parenterally as injections or orally as drops, i.e. by methods which are especially suitable in early infancy and adolescence, and, at the same time, it limits their availability to the living organism after oral administration and results in a relatively low, incomplete and non-uniform absorption.
Furthermore, the acidity of the known phenyl-alkanoic acids often induces intolerance effects and may even give rise to ulceration of the gastro-intestinal mucosa, with the risk of severe haemorrhages in patients with a predisposition thereto.
It is also known that a number of other acidic anti-inflammatory substances, for example aspirin, phenylbutazone, the derivatives of mefenamic acid and indomethacine, also show these undesired side-effects in an even more pronounced form.
The acute toxicity of the phenyl-alkanoic acids appears to be very low both in pharmacological use and in clinical use for humans, although an occasional increase in serum transaminases, the appearance of jaundice and other secondary effects, even though very rare, suggest the possibility, with some derivatives in this series, of hepatic damage which would induce a certain degree of caution in the prolonged treatment of patients who initially suffered from hepatic dysfunction.
We have now found that the important disadvantages of the phenyl-alkanoic acids could be substantially avoided by means of salification with basic amino acids, the salts thus obtained being stable and extremely soluble in water to give substantially neutral aqueous solutions.
Other salts which we initially considered were those with the alkali metals. These are also soluble in water but proved to be less suitable for therapeutic use due to their strongly basic pH and, in particular, because the high dosage level needed resulted in considerable amounts of the alkali metals also being administered, which are frequently contraindicated.